The activation of the sirtuin1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway has been shown to mitigate oxidative stress-induced apoptosis and mitochondrial damage by reducing reactive oxygen species (ROS) levels. Clinical trials have demonstrated that Zhongfeng Xingnao Liquid (ZFXN) ameliorates post-stroke cognitive impairment (PSCI). However, the underlying mechanism, particularly whether it involves protecting mitochondria and inhibiting apoptosis through the SIRT1/Nrf2/HO-1 pathway, remains unclear. This study employed an oxygen-glucose deprivation (OGD) cell model using SH-SY5Y cells and induced PSCI in rats through modified bilateral carotid artery ligation (2VO). The effects of ZFXN on learning and memory, neuroprotective activity, mitochondrial function, oxidative stress, and the SIRT1/Nrf2/HO-1 pathway were evaluated both in vivo and in vitro. Results indicated that ZFXN significantly increased the B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax) ratio, reduced terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL)⁺ cells, and markedly improved cognition, synaptic plasticity, and neuronal function in the hippocampus and cortex. Furthermore, ZFXN exhibited potent antioxidant activity, evidenced by decreased ROS and malondialdehyde (MDA) content and increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels. ZFXN also demonstrated considerable enhancement of mitochondrial membrane potential (MMP), Tom20 fluorescence intensity, adenosine triphosphate (ATP) and energy charge (EC) levels, and mitochondrial complex I and III activity, thereby inhibiting mitochondrial damage. Additionally, ZFXN significantly increased SIRT1 activity and elevated SIRT1, nuclear Nrf2, and HO-1 levels. Notably, these effects were substantially counteracted when SIRT1 was suppressed by the inhibitor EX-527 in vitro. In conclusion, ZFXN alleviates PSCI by activating the SIRT1/Nrf2/HO-1 pathway and preventing mitochondrial damage.
Sirtuin 1/genetics* ; Animals ; NF-E2-Related Factor 2/genetics* ; Cognitive Dysfunction/genetics* ; Male ; Rats, Sprague-Dawley ; Rats ; Humans ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Heme Oxygenase-1/genetics* ; Stroke/complications* ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Neuroprotective Agents

Triggering receptor expressed on myeloid cells 2 (TREM2)-mediated microglial phagocytosis is an energy-intensive process that plays a crucial role in amyloid beta (Aβ) clearance in Alzheimer's disease (AD). Energy metabolic reprogramming (EMR) in microglia induced by TREM2 presents therapeutic targets for cognitive impairment in AD. Jiawei Xionggui Decoction (JWXG) has demonstrated effectiveness in enhancing energy supply, protecting microglia, and mitigating cognitive impairment in APP/PS1 mice. However, the mechanism by which JWXG enhances Aβ phagocytosis through TREM2-mediated EMR in microglia remains unclear. This study investigates how JWXG facilitates microglial phagocytosis and alleviates cognitive deficits in AD through TREM2-mediated EMR. Microglial phagocytosis was evaluated through immunofluorescence staining in vitro and in vivo. The EMR level of microglia was assessed using high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits. The TREM2/protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway was analyzed using Western blotting in BV₂ cells. TREM2^-/- BV₂ cells were utilized for reverse validation experiments. The Aβ burden, neuropathological features, and cognitive ability in APP/PS1 mice were evaluated using ELISA kits, immunohistochemistry (IHC), and the Morris water maze (MWM) test. JWXG enhanced both the phagocytosis of EMR disorder-BV₂ cells (EMRD-BV₂) and increased EMR levels. Notably, these effects were significantly reversed in TREM2^-/- BV₂ cells. JWXG elevated TREM2 expression, adenosine triphosphate (ATP) levels, and microglial phagocytosis in APP/PS1 mice. Additionally, JWXG reduced Aβ-burden, neuropathological lesions, and cognitive deficits in APP/PS1 mice. In conclusion, JWXG promoted TREM2-induced EMR and enhanced microglial phagocytosis, thereby reducing Aβ deposition, improving neuropathological lesions, and alleviating cognitive deficits.
Drugs, Chinese Herbal/pharmacology* ; Microglia/drug effects* ; Phagocytosis ; Cognitive Dysfunction/drug therapy* ; Metabolic Reprogramming ; Animals ; Mice ; Cell Line ; Receptors, Immunologic/metabolism* ; Membrane Glycoproteins/metabolism* ; Signal Transduction ; Amyloid beta-Peptides/metabolism* ; Energy Metabolism

Objective:To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization (MR) method.Methods:Single nucleotide polymorphisms (SNP) strongly associated with 91 plasma inflammatory proteins in genome-wide association studies (GWAS) were used as instrumental variables, and liver cirrhosis was used as the outcome variable. Random-effects inverse variance-weighted (IVW), MR Egger regression, odds ratio ( OR) and its 95% confidence interval were used to evaluate the causal relationship. Simultaneously, sensitivity analysis was performed using MR pleiotropy residuals and outliers (MR-PRESSO) and the Q-test. Results:The causal relationship between the expression of seven specific circulating inflammatory proteins and liver cirrhosis was confirmed by the inverse variance-weighted (IVW) method. The results showed that five plasma inflammatory proteins, including leukemia inhibitory factor [ OR( CI)=0.66, P=9.73×10 -5], interleukin-18 [ OR( CI)=0.76, P=0.013], tumor necrosis factor ligand superfamily member 12[ OR( CI)=0.75, P=0.024], monocyte chemoattractant protein 2 [ OR( CI)=0.89, P=0.036], and C-C motif chemokine 25 [ OR( CI)=0.84, P=0.039], were negatively correlated with cirrhosis and were protective factors for cirrhosis. T cell surface glycoprotein CD5 [ OR ( CI)=1.29, P=0.035] and C-X-C motif chemokine 10 [ OR( CI)=1.32, P=0.043] were positively correlated with cirrhosis and were risk factors for cirrhosis. The results of the MR-PRESSO, Q-test, MR-Egger intercept test, and leave-one-out method all showed the stability. Conclusion:The research results indicated that the increased levels of leukemia inhibitory factor, interleukin-18, tumor necrosis factor ligand superfamily member 12, monocyte chemoattractant protein-2, and C-C motif chemokine 25 were protective factors in the development of cirrhosis, while the increased levels of T cell surface glycoprotein CD5 and C-X-C motif chemokine 10 were risk factors for the development of cirrhosis based on genetic data.

Objective:To investigate cerebral blood flow (CBF) changes in type 2 diabetes mellitus (T2DM) and its relationship with cognitive function by arterial spin labeling (ASL).Methods:This study was a cross-sectional study. Clinical data (age, sex, years of education, body mass index) and imaging data of 46 patients with T2DM (T2DM group) and 57 healthy controls (HC group), who visited the First Affiliated Hospital of Guangzhou University of Chinese Medicine from September 2017 to March 2019 were analyzed retrospectively. All subjects underwent clinical cognitive function assessments, including the auditory verbal learning test (AVLT), trail making test (TMT), and montreal cognitive assessment (MoCA) scale. All subjects underwent routine axial 3D-ASL imaging, and CBF pseudocolor images were automatically generated from the 3D-ASL raw images. CBF values in the differential brain regions were extracted. The differences in clinical data, cognitive function scores, and CBF values between T2DM group and HC group were evaluated using independent sample t-tests, Mann-Whitney U tests, and χ 2 tests. The correlation between the differential brain region CBF values and cognitive function scores was analyzed using partial correlation analysis, controlling for age, gender, and years of education. Results:There were no significant differences in age, gender, years of education, AVLT scores, and TMT scores between T2DM group and HC group ( P>0.05). But there were significant differences in body mass index and MoCA scores ( Z=-2.16, P=0.031; Z=-3.18, P=0.001). Compared with HC group, T2DM group showed significantly increased CBF in the left insula ( P<0.001), but significantly decreased CBF in the right fusiform gyrus, right cuneus, and right prefrontal gyrus ( P<0.001). The partial correlation analysis showed that the CBF value in the right prefrontal gyrus of T2DM group was positively correlated with MoCA scores ( r=0.330, P=0.001), while the CBF value in the right fusiform gyrus was positively correlated with MoCA scores ( r=0.210, P=0.034). Conclusions:Patients with T2DM show changes in CBF in the left insula, right fusiform gyrus, right cingulate anterior, and right prefrontal cortex. Reduced CBF in the right prefrontal cortex and right fusiform gyrus is associated with cognitive function decline.

Visual system is a critical sensory system in humans and a vital component of the central nervous system, which is responsible for over 80% of external information acquisition.Visual function is a key indicator of overall health.With socioeconomic development, the public has higher expectations for eye health, shifting the focus of eye health initiatives from disease treatment to comprehensive public eye health.Key scientific challenges include how to effectively prevent, diagnose, and treat blindness and visual impairment at an early stage; how to enhance the overall visual quality of patients to ensure not just sight but clear and comfortable vision; and how to meet the public's diverse and multi-tiered eye health needs.Visual science is an interdisciplinary field exploring the development of the visual system, the mechanisms of vision, and brain-related perceptual, cognitive and behavioral processes involving sight.Prioritizing and advancing visual science research is of great significance for promoting comprehensive eye health and implementing the Healthy China Strategy.This article first outlines the concept and research significance of visual science.It then highlights the key scientific questions in visual science pertaining to several major eye diseases, such as myopia, amblyopia, cataract, fundus diseases, glaucoma, and corneal diseases, reviews the historical foundation of visual science research in China, selectively summarizes key achievements and ongoing progress in this field, analyzes the landscape and challenges faced by domestic research, and proposes, to this end, strategies to advance visual science in China.These recommendations are designed to promote visual science research in China and ultimately advance comprehensive eye health.

Objective Study on the relationship between detection of 10 driver gene mutations in non-small cell lung cancer tis-sues and clinical pathological characteristics,as well as the diagnostic value of multi gene combined models.Methods Selected 79 patients diagnosed with NSCLC in Zhongshan People's Hospital from December 2022 to April 2023 as the research objects,collected tissue samples,used PCR technology for mutation detection,obtain the detection rate of each driver gene,and explore gene mutations and NSCLC patients correlation of clinicopathological characteristics.Logistic regression method was used to es-tablish a multi-gene joint model of joint predictors and evaluate its diagnostic value.Results Among the 79 cases,the total muta-tion rate of the ten driving genes was 81.01%(64/79),Among them the mutation rate of EGFR was 54.43%(43/79),the mutation frequency of KRAS was 13.92%(11/79),the mutation rate of HER2 was 3.80%(3/79),the fusion frequency of ALK was 2.53%(2/79),the fusion frequency of ROS1 was 2.53%(2/79),the mutation rate of MET was 2.53%(2/79),the mutation rate of NRAS was 1.27%(1/79),and no mutations were detected in RET,BRAF and PIK3CA.The mutation frequency of EGFR in fe-male patients was higher than that in males(χ2=20.512,P<0.001),ALK fusion was also more common in females(χ2=192.080,P<0.001),while KRAS was the opposite.The mutation frequency in male patients was higher than that in females(χ2=4.545,P<0.05).EGFR mutations were more common in individuals＜60 years old(χ2=33.907,P<0.001),while KRAS mutations had a higher individuals in patients≥60 years old than in those＜60 years old(χ2=8.909,P<0.001).The positive mutation of EGFR was more common in stage IV patients(χ2=15.429,P<0.001).ROS1 fusion is more common in stage III b patients(χ2=4.000,P<0.05),EGFR mutation had a significantly higher mutation rate in non-smoking patients than in smoking patients(χ2=50.651,P<0.001),and ALK fusion had a higher mutation rate in smoking patients than in non-smoking patients(χ2=4.000,P<0.05).Con-structed a Logistic regression model to evaluate the diagnostic value of driver gene joint detection,and constructed a Logistic re-gression model to predict the occurrence of NSCLC in patients.The model expression was:logit(P)=-0.190+0.168 EGFR muta-tion(X1)+0.516 KRAS mutation(X2)+0.331 ALK fusion(X3)+0.403 ROS1 fusion(X4)+0.429 NRAS mutation(X5)+0.515 HER2 mutation(X6)+0.405 MET mutation(X7).The ROC curve results show that the diagnostic value of the joint prediction model for NSCLC was higher than that of a single indicator.Conclusion There is a correlation between driver gene mutation status and pathological characteristics,and the co-mutation information provided by multi-gene joint detection can make a more accurate diagnosis of NSCLC.

Visual system is a critical sensory system in humans and a vital component of the central nervous system, which is responsible for over 80% of external information acquisition.Visual function is a key indicator of overall health.With socioeconomic development, the public has higher expectations for eye health, shifting the focus of eye health initiatives from disease treatment to comprehensive public eye health.Key scientific challenges include how to effectively prevent, diagnose, and treat blindness and visual impairment at an early stage; how to enhance the overall visual quality of patients to ensure not just sight but clear and comfortable vision; and how to meet the public's diverse and multi-tiered eye health needs.Visual science is an interdisciplinary field exploring the development of the visual system, the mechanisms of vision, and brain-related perceptual, cognitive and behavioral processes involving sight.Prioritizing and advancing visual science research is of great significance for promoting comprehensive eye health and implementing the Healthy China Strategy.This article first outlines the concept and research significance of visual science.It then highlights the key scientific questions in visual science pertaining to several major eye diseases, such as myopia, amblyopia, cataract, fundus diseases, glaucoma, and corneal diseases, reviews the historical foundation of visual science research in China, selectively summarizes key achievements and ongoing progress in this field, analyzes the landscape and challenges faced by domestic research, and proposes, to this end, strategies to advance visual science in China.These recommendations are designed to promote visual science research in China and ultimately advance comprehensive eye health.

Objective:To explore the surgical treatment strategies for Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures.Methods:A retrospective analysis was performed on the clinical data of 25 adult patients with Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures, admitted to the Upper Extremity Orthopaedics Department of Zhengzhou Orthopaedic Hospital from June 2013 to June 2023. There were 15 males and 10 females, with an average age of 43.5±14.7 years (range: 20-67 years). Among them, 5 cases were complicated with humeroulnar joint dislocation. The patients were divided into two groups: 17 cases were treated with open reduction and internal fixation (ORIF) of radial head fractures combined with ORIF of proximal ulnar fractures (open reduction group), and 8 cases were treated with radial head replacement combined with ORIF of proximal ulnar fractures (radial head replacement group). At the last follow-up, elbow joint range of motion was recorded, and pain, elbow function, and subjective upper limb function were evaluated using the Visual Analogue Scale (VAS), Mayo Elbow Performance Score (MEPS), and Disabilities of the Arm, Shoulder and Hand (DASH) scale. The incidence of complications was also recorded.Results:All 25 patients were followed up for an average of 25.6±9.0 months (range: 12-45 months). At the last follow-up, the affected elbows in the open reduction group had a flexion of 124.47°±12.59° (range, 90°-140°), extension of 21.12°±10.07° (range, 10°-50°), pronation of 48.59°±11.62° (range, 20°-61°), and supination of 48.53°±8.43° (range, 30°-60°). In the radial head replacement group, the affected elbows showed flexion of 128.75°±13.17° (range, 100°-140°), extension of 14.00°±7.71° (range, 0°-25°), pronation of 61.25°±10.26° (range, 60°-80°), and supination of 71.88°±10.33° (range, 60°-80°). The MEPS score in the open reduction group was 82(75, 85) points (range, 55-90 points), the VAS pain score was 1(1, 2) points (range, 0-3 points), and the DASH score was 9(8, 14) points. In the radial head replacement group, the MEPS score was 90(85, 90) points (range, 85-90 points), the VAS pain score was 1(0, 1) points (range, 0-1 points), and the DASH score was 5(5, 6) points. Complications included 5 cases of heterotopic ossification, 1 case of incision infection, 1 case of nonunion, 1 case of ulnar nerve injury combined with traumatic arthritis, and 1 case of proximal radioulnar bone bridge formation.Conclusions:Both radial head replacement and open reduction internal fixation combined with proximal ulnar fracture fixation can effectively treat Mason type III radial head fractures complicated with adult Bado type II Monteggia fractures. There was no significant difference in postoperative flexion and extension, but the radial head replacement group demonstrated better forearm rotation and DASH scores postoperatively.

Objective:To investigate the impact of the number of cesarean deliveries on adverse maternal and neonatal outcomes.Methods:A retrospective analysis was conducted on 11 904 singleton pregnant women who underwent cesarean delivery at the Third Affiliated Hospital of Guangzhou Medical University from January 1st, 2019 to December 31st, 2023. The women were grouped according to the number of cesarean deliveries: those undergoing their first cesarean delivery (1CD group, 7 231 cases), those undergoing their second cesarean delivery (2CD group, 3 749 cases), those undergoing their third cesarean delivery (3CD group, 841 cases), and those undergoing their fourth or more cesarean deliveries (4CD group, 83 cases). Differences in clinical characteristics, related surgical procedures, and adverse maternal and neonatal outcomes among the groups were compared. Binary logistic regression analysis was used to assess the impact of the number of cesarean deliveries on related surgical procedures and adverse maternal and neonatal outcomes.Results:(1) During the 5-year period, the total number of women undergoing cesarean delivery in our hospital showed a slight downward trend, while the proportion of women undergoing three or more cesarean deliveries increased. (2) Compared with women undergoing their first cesarean delivery, women in each repeat cesarean delivery group were older, had higher proportions of advanced maternal age and pre-pregnancy body mass index, and had more pregnancies, deliveries, and induced abortions; the incidence of placenta previa, placental implantation, antepartum hemorrhage, gestational hyperglycemia, and failed trial of labor requiring conversion to surgery was higher, while the incidence of premature rupture of membranes was lower; the proportions of ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and postoperative intestinal obstruction were higher, and the amount of postpartum hemorrhage was greater; the gestational age at delivery of neonates was earlier, but the rates of preterm birth at 28-31 +6 and 32-33 +6 weeks of gestation were lower; the differences were statistically significant ( P<0.05) for all comparisons. (3) The number of cesarean deliveries was not an independent risk factor for the dose-dependent occurrence of placenta previa (a OR=0.99, 95% CI: 0.98-1.01; P=0.261). In women without placenta previa, the number of cesarean deliveries was not a risk factor for placental implantation (a OR=1.12, 95% CI: 0.90-1.39; P=0.320). However, in women with placenta previa, the number of cesarean deliveries was a risk factor for placental implantation (a OR=4.01, 95% CI: 3.08-5.22; P<0.001). In the overall population, the number of cesarean deliveries was a risk factor for ureteral stent placement, adhesiolysis of the pelvic and abdominal cavities, bladder rupture repair, uterine rupture, uterine reconstruction, uterine artery ligation, hysterectomy, postpartum hemorrhage, and preterm birth (all P<0.05). However, the number of cesarean deliveries was not a risk factor for postoperative intestinal obstruction, admission to the intensive care unit, neonatal asphyxia, admission to the neonatal intensive care unit, or neonatal death (all P<0.05). Conclusions:The number of cesarean deliveries could lead to adverse maternal and neonatal outcomes, but the relationship is not simply dose-dependent. It is speculated that the occurrence of severe adverse maternal and neonatal outcomes is more closely related to maternal complications and comorbidities, as well as whether multidisciplinary comprehensive management was received.

Objective:To explore the efficacy of a new classification system proposed by us applied to the treatment of irreducible intertrochanteric femoral fractures.Methods:A retrospective study was conducted to analyze the clinical data of the 225 patients with irreducible intertrochanteric femoral fracture who had been treated between January 2023 and November 2024 at Zhengzhou Orthopedic Hospital (78 cases), The First Affiliated Hospital of Zhengzhou University (61 cases), Zhengzhou Central Hospital Affiliated to Zhengzhou University (28 cases), Zhengzhou Hospital of Traditional Chinese Medicine (34 cases), and Puyang Hospital of Traditional Chinese Medicine (24 cases). There were 86 males and 139 females, with an age of (74.8±7.9) years. Satisfactory reduction had failed in all patients even after 3 attempts at closed reduction. The patients were divided into 2 groups based on whether the new classification system proposed by our research team in our previous study was used to guide the treatment. The observation group of 116 cases were treated through an extended incision at the head of the intramedullary nail for reduction and fixation under the guidance of the new classification system while the control group of 109 cases were treated by reduction and fixation through a direct anterolateral incision. The operation time, intraoperative blood loss, fracture healing time, Harris hip scores at 3 months after operation and the last follow-up, and incidence of complications were compared between the 2 groups.Results:No statistically significant differences were observed in the baseline characteristics between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (12.6±2.5) months after operation. The operation time, intraoperative blood loss, and fracture healing time [(39.5±9.7) minutes, (106.6±54.8) mL, and (3.1±0.7) months] in the observation group were significantly less than those in the control group [(70.2±11.1) minutes, (322.8±55.5) mL, and (4.5±0.7) months] ( P<0.05). The Harris hip scores at 3 months after operation and the last follow-up in the observation group [(90.3±3.4) points and (93.7±3.2) points] were significantly higher than those in the control group [(75.1±3.8) points and (78.7±3.6) points] ( P<0.05). The incidence of complications in the observation group was 6.0% (7/116), significantly lower than that in the control group [14.7% (16/109)] ( P<0.05). Conclusion:In the treatment of irreducible intertrochanteric femoral fractures, compared with the conventional anterolateral approach for intramedullary nailing, the extended intramedullary head nail approach guided by our new classification system can reduce operation time, intraoperative blood loss, fracture healing time, and incidence of postoperative complications, and improve postoperative hip joint function.